Device and Method for Simulation of Surface Bleedings

ABSTRACT

The invention relates to a device to simulate a surface bleeding, comprising: —A source of a blood liquid, in particular a synthetic blood liquid or a blood liquid having been removed from a human body; A pump system connected to the source of blood liquid and configured to provide a controlled flow of said blood liquid; A wound simulator having an open chamber connected to the pump system to receive the controlled flow of blood liquid, wherein the wound simulator comprises a set of interchangeable plates, each plate having a plurality of holes arranged through said plate according to a specific pattern, wherein the specific pattern is different for each plate of the set of interchangeable plates, and. each plate being adapted to be removably mounted on the wound simulator to close the open chamber, so that blood liquid flows out of the chamber through the holes of the plate mounted on the wound simulator. The invention also relates to methods of use of such simulating device.

FIELD OF THE INVENTION

The invention relates to the medical field and more particularly theassessment of the severity of a surface bleeding, for example todetermine the efficacy of a hemostatic agent on a wound.

TECHNICAL BACKGROUND

Assessment of the efficacy of a product, in particular a medicalproduct, is meaningful when the protocol for validating one particularproduct is reliable and repeatable in a consistent and comparablemanner.

Such reliable and repeatable protocols are however not always available.For instance, the evaluation of the hemostatic performance of a productis very difficult as there is no method available for consistentassessment of the bleeding severity of wounds. In addition, there is nomethod available that would be applicable to any surgical procedure foruse for example in a clinical investigation assessing the performance ofthe hemostatic agent.

An estimate of total intraoperative blood loss is an integral part ofany surgical procedure and is considered routine care. The wide varietyof surgical specialties and operations make quantitative standardizationof total blood loss difficult, yet estimates may still be provided.Estimating total blood loss during a surgical procedure, supplementedwith other variables such as blood pressure, are data helpful for theongoing evaluation of the condition of a subject and theassessment/modification of intra- and post-operative management.

Adams et al. have described a sketched scale in the publication entitled“Acute in-vivo evaluation of bleeding with Gelfoam plus saline andGelfoam plus human thrombin using a liver square lesion model in swine”(J Thromb Thrombolysis. 2009 July; 28(1):1-5. doi:10.1007/s11239-008-0249-3. Epub 2008 Jul. 16) used for assessinghemostasis or residual bleeding after placement of a product, inparticular Gelfoam (which is produced by Baxter). There is however noindication of how bleeding severity is established duringintra-operative inclusion/exclusion assessment before randomization, inparticular before investigational device placement. Such scale furtherappears not to be adapted to be used consistently to assesssuccess/failure of a product vs. hemostasis. This proposed scale doesnot include the full range of potential input and output domain datavalues for each proposed site, e.g. it does not include or distinguishlife threatening as well as severe bleeding.

There does not appear to be correlation of the amount of bloodassociated with any score at any site to an objective measure of thisamount of blood, e.g. weight of blood loss over a pre-specified time.There is thus a need for a score representative of a comparable amountof blood mass or flow across the various anatomic sites and undervarious potentially significant conditions (covariates).

A goal of the invention is to propose a system and method to simulatesurface bleedings and validate a bleeding severity assessment scale forfurther application, during surgery and/or in clinical trials forexample.

A goal of the invention is in particular to provide a method thatenables establishing a bleeding severity during intra-operativeinclusion/exclusion assessment before randomization and investigationaldevice placement.

Another goal of the invention is to provide a surface bleeding severityscale to be used for the consistent assessment of hemostatic success orfailure. It would preferably include the full range of any potentialinput and output domain data values expected for bleeding severitiesseen during elective surgical procedures.

A further goal of the invention is to provide a system and method tocreate a surface bleeding model allowing for consistency in theassessments of success/failure of hemostasis, while not being dependenton an individual animal physiology.

Still another goal of the invention is to provide a system and method toensure consistency of bleeding severity assessments across investigatorstesting a particular product, in particular in a clinical investigation,to ensure notably that similar bleeding severities are enrolled duringthe investigation.

A specific goal of the invention is to provide a system and method to beused during a clinical study of a hemostatic product, in particular todetermine intraoperative eligibility of patients, as well as hemostaticsuccess of the tested product. In particular a goal is to ensureconsistent enrollment of target bleeding sites of bleeding severities tobe treated for assessment of the hemostatic product under investigationand help ensure subject safety by excluding those who have a too severebleeding.

Still another goal on the invention is to provide a system and method tohelp training and testing investigators to recognize a specific degreeof surface bleeding and homogeneously assess such surface bleeding in aclinical investigation.

SUMMARY OF THE INVENTION

To this end, is proposed a device to simulate a surface bleeding andcorresponding method as defined in the appended claims.

The following numbered examples describe features in accordance withvarious embodiments of the invention as further described above.

Example 1 relates to a device to simulate a surface bleeding,comprising:

-   -   A source of a blood liquid, in particular a synthetic blood        liquid or a blood liquid having been removed from a human body;    -   A pump system connected to the source of blood liquid and        configured to provide a controlled flow of said blood liquid;    -   A wound simulator having an open chamber connected to the pump        system to receive the controlled flow of blood liquid, wherein        the wound simulator comprises a set of interchangeable plates,        -   each plate having a plurality of holes arranged through said            plate according to a specific pattern, wherein the specific            pattern is different for each plate of the set of            interchangeable plates, and        -   each plate being adapted to be removably mounted on the            wound simulator to close the open chamber, so that blood            liquid flows out of the chamber through the holes of the            plate mounted on the wound simulator.

Example 2 relates to the device of Example 1, wherein the plates of theset of interchangeable plates have holes arranged according to specificpatterns of different surface areas, in particular of different sizes.

Example 3 relates to the device of any one of Examples 1 or 2, whereinthe holes are provided in each of the interchangeable plates at adensity of at least 50 holes/cm², and preferably of 100 holes/cm².

Example 4 relates to the device of any one of Examples 1 to 3, whereinthe number and diameter of the holes provided in each of theinterchangeable plates are set to reproduce the visual appearance of ableeding surface.

Example 5 relates to the device of Example 4, wherein the holes providedin each one of the interchangeable plates have all the same diameter,preferably comprised between 0.2 mm and 1 mm, and most preferably of 0.5mm.

Example 6 relates to the device of any one of Examples 1 to 5, whereinthe holes provided in each one of the interchangeable plates areregularly spaced apart in the corresponding specific pattern, with apitch preferably comprised between 0.4 mm and 2 mm, and most preferablyof 1 mm.

Example 7 relates to the device of any one of Examples 1 to 6, whereinthe wound simulator further comprises a gravity fed gutter system todrain out the blood liquid having passed through the holes of the plateand guide it into a receiving container.

Example 8 relates to the device of any one of Examples 1 to 7, furthercomprising a pressure monitoring system connected to the pump system tomeasure the pressure of the blood liquid supplied to the open chamber ofthe wound simulator.

Example 9 relates to the device of any one of Examples 1 to 8, whereinthe pump system comprises a peristaltic pump provided with tubing forcirculation of the blood liquid from the blood source to the openchamber.

Example 10 relates to the device of any one of Examples 1 to 9, whereinthe pump system comprises a pump controller for control of the flow ofthe blood liquid from the blood source to the open chamber.

Example 11 relates to a method for simulating a plurality of differentsurface bleedings with for instance the device of any of Examples 1 to10, wherein each surface bleeding is simulated by mounting on the woundsimulator a specific plate chosen among the set of interchangeableplates, and adjusting the flow of blood liquid provided by the pumpsystem to a specific value.

Example 12 relates to the method of Example 10, comprising thesimulation of several sets of surface bleedings, wherein:

-   -   a first set of surface bleedings is simulated to represent a        first degree of severity of surface bleeding, each of the        surface bleedings being simulated by adjusting the flow of the        blood liquid provided by the pump system to a specific value        being chosen superior to 0 mL/min and inferior to 4.8 mL/min;    -   a second set of surface bleedings is simulated to represent a        second degree of severity of surface bleeding, each of the        surface bleedings being simulated by adjusting the flow of the        blood liquid provided by the pump system to a specific value        being chosen superior or equal to 4.8 mL/min and inferior to        12.0 mL/min.    -   a third set of surface bleedings is simulated to represent a        third degree of severity of surface bleeding, each of the        surface bleedings being simulated by adjusting the flow of the        blood liquid provided by the pump system to a specific value        being chosen superior or equal to 12.0 mL/min and inferior to        25.3 mL/min.    -   a fourth set of surface bleedings is simulated to represent a        fourth degree of severity of surface bleeding, each of the        surface bleedings being simulated by adjusting the flow of the        blood liquid provided by the pump system to a specific value        being chosen superior or equal to 25.3 mL/min and inferior to        102.0 mL/min.    -   a fifth set of surface bleedings is simulated to represent a        fifth degree of severity of surface bleeding, each of the        surface bleedings being simulated by adjusting the flow of the        blood liquid provided by the pump system to a specific value        being chosen superior or equal to 102.0 mL/min.

Example 13 relates to the method of Example 10, comprising thesimulation of several sets of surface bleedings, wherein:

-   -   a first set of surface bleedings is simulated to represent a        first degree of severity of surface bleeding, said first set of        surface bleedings comprising        -   at least one surface bleeding being simulated by mounting a            plate with through holes arranged according to a pattern of            1 cm² and by adjusting the flow of the blood liquid provided            by the pump system to a specific value being chosen superior            to 0 mL/min and inferior to 4.8 mL/min;        -   at least one surface bleeding being simulated by mounting a            plate with through holes arranged according to a pattern of            10 cm² and by adjusting the flow of the blood liquid            provided by the pump system to a specific value being chosen            superior to 0 mL/min and inferior to 9.1 mL/min;        -   at least one surface bleeding being simulated by mounting a            plate with through holes arranged according to a pattern of            50 cm² and by adjusting the flow of the blood liquid            provided by the pump system to a specific value being chosen            superior to 0 mL/min and inferior to 13.5 mL/min;    -   a second set of surface bleedings is simulated to represent a        second degree of severity of surface bleeding, said second set        of surface bleedings comprising        -   at least one surface bleeding being simulated by mounting a            plate with through holes arranged according to a pattern of            1 cm² and by adjusting the flow of the blood liquid provided            by the pump system to a specific value being chosen superior            or equal to 4.8 mL/min and inferior to 12.0 mL/min;        -   at least one surface bleeding being simulated by mounting a            plate with through holes arranged according to a pattern of            10 cm² and by adjusting the flow of the blood liquid            provided by the pump system to a specific value being chosen            superior or equal to 9.1 mL/min and inferior to 20.0 mL/min;        -   at least one surface bleeding being simulated by mounting a            plate with through holes arranged according to a pattern of            50 cm² and by adjusting the flow of the blood liquid            provided by the pump system to a specific value being chosen            superior or equal to 13.5 mL/min and inferior to 28.0            mL/min;    -   a third set of surface bleedings is simulated to represent a        third degree of severity of surface bleeding, said third set of        surface bleedings comprising        -   at least one surface bleeding being simulated by mounting a            plate with through holes arranged according to a pattern of            1 cm² and by adjusting the flow of the blood liquid provided            by the pump system to a specific value being chosen superior            or equal to 12.0 mL/min and inferior to 25.3 mL/min;        -   at least one surface bleeding being simulated by mounting a            plate with through holes arranged according to a pattern of            10 cm² and by adjusting the flow of the blood liquid            provided by the pump system to a specific value being chosen            superior or equal to 20.0 mL/min and inferior to 71.3            mL/min;        -   at least one surface bleeding being simulated by mounting a            plate with through holes arranged according to a pattern of            50 cm² and by adjusting the flow of the blood liquid            provided by the pump system to a specific value being chosen            superior or equal to 28.0 mL/min and inferior to 117.3            mL/min;    -   a fourth set of surface bleedings is simulated to represent a        fourth degree of severity of surface bleeding, said fourth set        of surface bleedings comprising        -   at least one surface bleeding being simulated by mounting a            plate with through holes arranged according to a pattern of            1 cm² and by adjusting the flow of the blood liquid provided            by the pump system to a specific value being chosen superior            or equal to 25.3 mL/min and inferior to 102.0 mL/min;        -   at least one surface bleeding being simulated by mounting a            plate with through holes arranged according to a pattern of            10 cm² and by adjusting the flow of the blood liquid            provided by the pump system to a specific value being chosen            superior or equal to 71.3 mL/min and inferior to 147.4            mL/min;        -   at least one surface bleeding being simulated by mounting a            plate with through holes arranged according to a pattern of            50 cm² and by adjusting the flow of the blood liquid            provided by the pump system to a specific value being chosen            superior or equal to 117.3 mL/min and inferior to 192.7            mL/min;    -   a fifth set of surface bleedings is simulated to represent a        fifth degree of severity of surface bleeding, said fifth set of        surface bleedings comprising        -   at least one surface bleeding being simulated by mounting a            plate with through holes arranged according to a pattern of            1 cm² and by adjusting the flow of the blood liquid provided            by the pump system to a specific value being chosen superior            or equal to 102.0 mL/min;        -   at least one surface bleeding being simulated by mounting a            plate with through holes arranged according to a pattern of            10 cm² and by adjusting the flow of the blood liquid            provided by the pump system to a specific value being chosen            superior or equal to 147.4 mL/min;        -   at least one surface bleeding being simulated by mounting a            plate with through holes arranged according to a pattern of            50 cm² and by adjusting the flow of the blood liquid            provided by the pump system to a specific value being chosen            superior or equal to 192.7 mL/min.

Example 14 relates to the method of any one of Examples 11 to 13,wherein each of the simulated surface bleedings is recorded as a video.

Example 15 relates to method of preparation of at least a training setof videos comprising the following subsequent steps:

-   -   Selecting a plurality of videos of simulated surface bleedings        recorded for instance pursuant to the method of Example 14,        wherein a score corresponding to a degree of severity of surface        bleeding is affected to each one of the selected videos;    -   Classifying the selected videos in a specific order for        visualization, wherein the score of each of the videos is to be        displayed with the corresponding video.

Example 16 relates to the method of Example 15, wherein the videos areclassified for visualization according an increasing or decreasing orderof the corresponding degrees of severity of surface bleeding.

Example 17 relates to a method of preparation of at least a testing setof videos comprising the following subsequent steps:

-   -   Selecting a plurality of videos of simulated surface bleedings        recorded for instance pursuant to the method of Example 14,        wherein a score corresponding to a degree of severity of surface        bleeding is affected to each one of the plurality of videos;    -   Classifying the videos in a random order for visualization,        wherein the score of each of the videos is not to be displayed        with the corresponding video.

Example 18 relates to a method of preparation of at least a training setof videos and at least a testing set of videos using a plurality ofvideos of simulated surface bleedings recorded for instance pursuant tothe method of Example 14, wherein a score corresponding to a degree ofseverity of surface bleeding is affected to each one of the plurality ofvideos, comprising:

-   -   preparing the training set of videos by selecting some videos of        the plurality of videos, and classifying the selected videos in        a specific order for visualization, wherein the score and        information on the specific chosen plate of each of the videos        are to be displayed with the corresponding video;    -   preparing the testing set of videos by selecting some videos of        the plurality of videos, and classifying the selected videos in        a random order for visualization, wherein the score of each of        the videos is not to be displayed with the corresponding video,        and wherein the selection and/or classification of the videos is        different from the training set of videos.

Example 19 relates to a method of training a person to recognize andclassify a severity of a surface bleeding comprising the step ofdisplaying a plurality of training videos in a specific order, whereineach one of the training videos shows a simulated surface bleeding and ascore corresponding to the severity of said simulated surface bleeding.

Example 20 relates to the method of Example 19, wherein the trainingvideos are displayed according to an increasing or decreasing order ofthe corresponding degrees of severity of surface bleeding.

Example 21 relates to the method of any one of Examples 19 or 20,comprising a subsequent step of testing the person in applying thefollowing steps:

-   -   displaying in a random order a plurality of testing videos each        numerically labeled in sequence, wherein each one of the testing        videos shows a simulated surface bleeding without any score        corresponding to the severity of said simulated surface bleeding        of simulated surface bleeding, and wherein the testing videos        are different from the training videos and/or used in a        different order;    -   requesting the person to give for each of the testing videos a        score representative of the severity of the corresponding        surface bleeding in the order of the numerically labeled        sequence.

Example 22 relates to a method of performing a clinical trial to assesshemostatic power of a product against surface bleeding, comprising thefollowing steps:

-   -   a) characterizing the severity of a baseline surface bleeding        from a wound of a patient by affecting a score, said        characterization being for instance based on the training        performed according to any one of Examples 19 to 21;    -   b) applying the product on the wound according to a specific        protocol of use of the product;    -   c) at a predetermined time after step b), characterizing the        severity of the remaining surface bleeding from the wound of the        patient by affecting a score, said characterization being for        instance based on the training performed according to any one of        Examples 19 to 21.

Example 23 relates to the method of Example 22, wherein steps b) and c)are repeated several times after each characterization of the severityof the remaining surface bleeding in order to assess the hemostaticpower of the product over time.

BRIEF DESCRIPTION OF THE DRAWINGS

Other characteristics and advantages of the invention will become clearfrom the following description which is only given for illustrativepurposes and is in no way limitative and should be read with referenceto the attached drawings on which:

FIG. 1 is a schematic representation of a device for simulating asurface bleeding;

FIG. 2 is a perspective view of a wound simulator of the deviceillustrated in FIG. 1;

FIG. 3 is a perspective view illustrating a cross section of the woundsimulator of FIG. 2;

FIG. 4 is an enlarged perspective view in cross-section of the openchamber and gutter system of the wound simulator of FIG. 3;

FIG. 5 is an enlarged perspective view of one interchangeable plate ofthe wound simulator of FIG. 2;

FIG. 6a is an upper view of an interchangeable plate according to afirst embodiment;

FIG. 6b is a cross-section view of the interchangeable plate of FIG. 6aalong line A-A;

FIG. 7a is an upper view of an interchangeable plate according to asecond embodiment;

FIG. 7b is a cross-section view of the interchangeable plate of FIG. 7aalong line B-B;

FIG. 8a is an upper view of an interchangeable plate according to athird embodiment;

FIG. 8b is a cross-section view of the interchangeable plate of FIG. 8aalong line C-C.

DETAILED DESCRIPTION OF THE INVENTION

The following description is focused on the determination, recognitionand assessment of a surface bleeding, in particular to determine theseverity of such surface bleeding. All the corresponding teaching couldhowever be applied to any secretion of body fluid, in particular anysecretion of body fluid that has to be recognised and/or assessed formedical or scientific purposes, such as for example the bile.

Reliable and repeatable assessment of a surface bleeding needsestablishment of a scale that enables recognition of the severity of thesurface bleeding for any target bleeding site (TBS) that can be usedsimilarly for any surgical specialties, i.e. independently from theconsequence of the blood loss in such a specific surgical specialty.

Such scale—referred to SBSS for Surface Bleeding Severity Scale—willenable a consistent assessment of bleeding that is applicable to anysurgical procedure, to be used for instance in a clinical investigationassessing the performance of a medical product, such as a hemostaticagent.

In the case of a hemostatic agent, the goal is to ensure that thehemostat is applied when control of bleeding by conventional proceduresis ineffective or impractical and to allow severity of bleeding to bechosen for designed efficacy of a hemostatic product.

It is also important to ensure consistency of bleeding severityassessments across investigators and that only eligible bleedingseventies are enrolled during a clinical trial.

Device for Simulation of a Surface Bleeding

For building such a scale to assess the severity of intraoperativebleeding at a target bleeding site (TBS), it is proposed to use a deviceto simulate a surface bleeding, thus creating a bench-top bleedingmodel.

Specific use of this bench-top bleeding model enables simulating severalchosen types of bleeding so that a scale of surface bleeding severity isbuilt for later assessment by surgeons of a surface bleeding in a targetbleeding site.

Moreover, the specific device to simulate a surface bleeding enablesestablishing a correspondence between constant blood flow rate (andresulting blood volume in a defined period of time) and the developedsurface bleeding severity scale.

Thanks to such surface bleeding simulating device, it is possible totrain and test surgeons for assessment of any surface bleeding. Inparticular, this will be useful to train and test a surgeon investigatorthat would have to assess a surface bleeding for testing a hemostaticproduct for instance.

More generally, the surface bleeding simulating device helps people, inparticular surgeons, to learn how to assess the severity of surfacebleeding in any surgical situation, independently from the individualanimal physiology.

As illustrated in FIG. 1, the proposed device for simulating a surfacebleeding comprises a source 1 of a blood liquid. Such blood liquid canbe a synthetic blood liquid, a blood liquid having been removed from ahuman body, or any other liquid suitable to mimic blood.

One can for instance use the synthetic blood liquid commercialized byJeulin, a company located in France, under the reference “Sangsynthétique—ref: 107175”. This synthetic blood has the advantages ofhaving the similar color and viscosity as human blood, while beingeasily washable.

In the synthetic blood, one can preferably add between 1% and 30% byweight, and more preferably between 2% and 15% by weight, of asurfactant to adapt surface tension of the synthetic blood and to enablehomogeneous flow in the device. One example of surfactant that can beused is the product commercialized by Procter&Gamble under the tradename “Fairy Original” with the product code PA00168831. Such surfactantcomprises from 20% to 30% of a mixture of Alcohols, C10-16, ethoxylated,sulfates, sodium salts, and from 5% to 10% of a mixture of Amines,C10-16-alkyldimethyl, N-oxides.

When it is chosen to use blood liquid having been removed from a humanbody, it will be preferably treated to avoid coagulation, by using forexample Ethylenediaminetetraacetic acid (EDTA) or citrate.

Preferably, the temperature of the blood liquid is controlled to be at atemperature close to the human body temperature, i.e. around 37° C.Alternatively, the simulation can be done at room temperature, i.e. theblood liquid is at a temperature between 20° C. and 25° C.

The simulating device further comprises a pump system 2 connected to thesource 1 of blood liquid via a specific tubing system 4.

This pump system 2 is configured to provide a controlled flow F_(in) ofsaid blood liquid. Preferably the pump system 2 is adapted for providinga pulsated flow of blood liquid.

Preferably, the pump system 2 comprises a peristaltic pump 21 providedwith the tubing 4 necessary for circulation of the blood liquid from theblood source 1 at the required flow rate F_(in).

The pump system 2 may also preferably include a pump controller 22 forfull control of the flow of blood liquid within the tubing 4 of thesimulating device, in particular, the volume, flow rate, direction ofthe blood liquid.

The flow F_(in) of the blood liquid can be controlled to vary regularly,preferably with increments of at least 0.1 mL/min.

The tubing 4 is adapted to the flow range for which the pump system isintended to be used.

Preferably, the pump system 2 and corresponding tubing 4 are adapted forflow up to 500 mL/min, and most preferably up to 250 mL/min.

One could for instance use a pump system of the Allegro™ family,commercialized by KD Scientific, which combines a peristaltic pumpsystem with a controller unit.

According to a specific embodiment, the tubing 4 is specifically chosendepending on the flow rate that is to be used. For example, a first setof tubing 4 can be used for any flow rate up to 60 mL/min, whereas asecond set of tubing 4 is used for any flow rate above 60 mL/min. Forinstance, silicon tubes commercialized under the reference “Masterflex®L/S® 14” could be used for flow rates up to 60 mL/min, and silicon tubescommercialized under the reference “Masterflex® L/S® 25” could be usedfor flow rates above 60 mL/min.

The simulating device further comprises a wound simulator 3 having anopen chamber 31 connected to the pump system 4 to receive the controlledflow F_(in) of blood liquid

The wound simulator 3 comprises a set of interchangeable plates 32wherein each plate 32 is adapted to be removably mounted on the woundsimulator 3 to close the open chamber 31.

As illustrated in FIG. 5, each plate 32 has preferably a plurality ofholes 321 arranged through said plate 32 according to a specificpattern.

As a consequence, the blood liquid entering the chamber 31 via the fluidinlet 311, at a specific flow F_(in) controlled by the pump system 2,flows out of the chamber 31 through the holes 321 of the plate 32mounted on the wound simulator 3 (see flow F_(out) on FIG. 1).

The blood liquid flowing out of the holes 321 of the plate 32 mimics asurface bleeding, wherein the intensity of the simulated bleedingdepends on several parameters as for instance the controlled flow F_(in)of the blood liquid and the arrangement of the holes 321 through theplate 32.

Preferably, the specific pattern of arrangement of the through holes 321is different for each plate 32 of the set of interchangeable plates.This enables simulating different bleeding surface areas that couldcorrespond to standard target bleeding sites that a surgeon may comeacross during a surgery.

The patterns of arrangement are said to be different from one anotherfor instance if they have different shapes (square, rectangular,circular or any other more complex shape), if they have different sizes,and/or if the through holes 321 that are provided have differentdimensions.

FIGS. 6a, 6b, 7a, 7b, 8a and 8b illustrate for instance three differentplates 32 included in a set of plates, where the holes 321 are arrangedaccording to three different patterns P1, P2, and P3 respectively. Inthis case, the patterns differ from one another in that they havedifferent sizes.

Preferably, the density and diameter of the holes 321 provided in eachof the interchangeable plates are set to mimic the visual appearance ofa bleeding surface.

In particular, the holes can be provided in each of the interchangeableplates at a density of at least 50 holes/cm², and preferably a densityof 100 holes/cm².

The diameter of the through holes 321 can be constant, for instancecomprised between 0.2 mm and 1 mm, and is most preferably of 0.5 mm. Adiameter of 0.5 mm for the hole is indeed preferred as it represents thetypical size of small blood vessels.

The holes 321 provided may be regularly spaced apart in thecorresponding specific pattern, with a pitch preferably comprisedbetween 0.4 mm and 2 mm, and most preferably of 1 mm.

In the specific embodiments of the plates illustrated in FIGS. 6a, 6b,7a, 7b, 8a and 8b , the through holes 321 have all the same diameter of0.5 mm, and are regularly spaced apart (pitch of 1 mm/density of 100holes/cm²) according to a square pattern. The only difference betweenthe three plates of these embodiments is the size of the area of thesquare pattern.

The plate 32 of FIGS. 6a and 6b corresponds to the plate with theso-called small pattern, the pattern being a square of 1 cm². Such platecomprises 100 holes of a 0.5 mm diameter.

The plate 32 of FIGS. 7a and 7b corresponds to the plate with theso-called medium pattern, the pattern being a square of 10 cm². Suchplate comprises around 1000 holes (more precisely 961 holes) of a 0.5 mmdiameter.

The plate 32 of FIGS. 8a and 8b corresponds to the plate with theso-called large pattern, the pattern being a square of 50 cm². Suchplate comprises around 5000 holes (more precisely 5041 holes) of a 0.5mm diameter.

This specific set of interchangeable plates 32 is especially preferredfor the simulation of surface bleeding as it corresponds to the size ofseveral different wounds which will enable having representative data tobuild a surface bleeding scale.

Other examples of possible plates to be used alone or in combination ofthe above mentioned plates to form a set of plates are the following:

-   -   a plate with a square pattern of 5 cm², comprising around 500        holes of a 0.5 mm diameter;    -   a plate with a square pattern of 20 cm², comprising around 2000        holes of a 0.5 mm diameter;    -   a plate with a square pattern of 50 cm², comprising around 200        holes of a 0.5 mm diameter.

Preferably the holes 321 are drilled in the plates 32 according to therequired pattern.

The plates are preferably made in a material chosen so that thecorresponding surface tension participates to the homogeneous surfaceflow of the blood liquid passing through the holes, thereby simulatingan homogeneous bleeding.

When a surfactant is used in a synthetic blood liquid, the quantitythereof is preferably controlled depending on the hydrophobic featuresof the material, and thus on the surface tension resulting from thechosen material.

The plates 32 may for example be made of acrylic, plexiglass, orPolymethyl-methacrylate (PMMA).

Alternatively or additionally, the plates 32 may be formed in a materialhaving a specific porosity so that liquid can pass through the plate.The porosity is chosen so that it opposes a resistance to the passage offluid, in order to mimic the capillarity of a surface vessel, vein, orartery.

Preferably the color of the plates is also chosen specifically dependingof the surface bleeding which is to be simulated. For instance, forsimulating a surface bleeding from an organ (e.g. the liver), the platesare preferably colored in red, or made in a material being red. Forsimulating a bleeding from a bone, a white plate could be used. Forsimulating a bleeding from fat, a yellow plate could be used. Moregenerally, the plate could have the color of the targeted tissue.

In a preferred embodiment, the color of the plates is chosen to mimicthe worst case-scenario that could happen in a surgery in terms ofcontrast between the blood and the bleeding surface (for instance ableeding from the liver where the contrast is low). In such case, theplates are thus preferably colored in red, or made in a material beingred.

Preferably, the wound simulator 3 further comprises a gutter system 34to drain out the blood liquid having passed through the holes 321 of theplate 32. This gutter system can be an overflow gutter 341 asillustrated in FIG. 4.

The gutter system 34 is preferably designed to guide the blood liquidfrom the plate 32 into a receiving container 33, which is for instanceplaced in the wound simulator 3 under the open chamber 31, such that itis fed by gravity (see flow F_(G) on FIG. 1). In this case, the guttersystem 34 can comprise a funnel-shaped element 342, which is forinstance vacuum formed.

The receiving container 33 may for example comprise a wide neck returnbottle, that can be made in high density polyethylene (HDPE).

The volume of the receiving container 33 is preferably chosen to belarge enough to avoid having to change it during the simulation of oneparticular surface bleeding. Preferably, the receiving container 33 hasa volume of at least 1 L.

In another embodiment, the receiving container 33 is connected to thesource 1 of blood liquid so as to form a closed loop for the bloodliquid to circulate within the simulating device. In such case, filtermeans are preferably interposed between the receiving container 33 andthe source 1 of blood liquid to remove any impurities that could havepolluted the blood liquid having passed through the holes 321 of theplate 32.

According to one specific embodiment, most of the elements forming thewound simulator 3 are made in polycarbonate. A support structuremanufactured in aluminium can in this case be provided to stabilize thewound simulator.

The device for simulating surface bleedings can also include a pressuremonitoring system 5 connected to the pump system 2 to measure thepressure of the blood liquid supplied to the open chamber 31 of thewound simulator 3. The pressure monitoring system 5 enables controllingthat the flows of blood liquid used for surface bleeding simulationsremain at physiologic ranges of pressure.

Such device is very advantageous for simulating several types of surfacebleedings, and for consequently building a corresponding scale to enablesorting surface bleedings depending on their severity as assessed bysurgeons of reference.

In particular, a plurality of different surface bleedings can besimulated with such device by mounting on the wound simulator 3 aspecific plate 32 chosen among the set of interchangeable plates andadjusting the flow of blood liquid provided by the pump system 2 to aspecific value.

Method for Building a Surface Bleeding Severity Scale

Below is described one specific method for building a surface bleedingseverity scale by using the above described simulating device.

First, easy-to-understand commonly used terms to qualify and describethe severity of surface bleedings have been selected to create thefollowing qualitative 6-point ordinal scale for surface bleeding:

0—No bleeding/hemostasis

1—Minimal bleeding

2—Mild bleeding

3—Moderate bleeding

4—Severe bleeding

5—Extreme bleeding

In addition to those verbal descriptors of the surface bleedings, avisual descriptor has been assigned for each of the scores of the scale,as well as an expected intervention for a surgeon. Table 1 belowsummarizes the features of the proposed surface bleeding scale.

TABLE 1 Surface Bleeding Severity Score 0 1 2 3 4 5 Verbal None MinimalMild Moderate Severe; not Extreme; Descriptor of immediately immediatelythe bleeding life-threatening life-threatening Visual Dry Oozing PoolingFlowing Streaming Gushing Descriptor of the bleeding Expected NoneManual pressure, Manual pressure, Manual pressure, Manual pressure,Manual pressure, Intervention(s) cautery, adjuvant cautery, suture,cautery, suture, cautery, suture, cautery, suture, hemostat(s) adjuvanthemostat(s) adjuvant hemostat(s) staples, tissue staples, tissue repairrepair Maximum 1 1 1 2 3 4 Expected ACS-ATLS Shock Risk Class

In the above table, the Shock Risk scale of ACS-ATLS (American Collegeof Surgeons—Advanced Trauma Life Supports) is defined as follows:

-   -   Class 1: involves up to 15% of blood volume; typically no charge        in vital signs and fluid resuscitation is not usually necessary.    -   Class 2: involves 15-30% of total blood volume; patient is often        tachycardic with a narrowing of the difference between the        systolic and diastolic blood pressures; the body attempts to        compensate with peripheral vasoconstriction; skin may start to        look pale and be cool to the touch; volume resuscitation with        crystalloids is all that is typically required; blood        transfusion is not typically required.    -   Class 3: involved loss of 30-40% of circulating blood volume;        patient's blood pressure drops; heart rate increases, peripheral        hypoperfusion worsens; fluid resuscitation with crystalloid and        blood transfusion are usually necessary.    -   Class 4: involves loss of more than 40% of circulating blood        volume; the limit of the body's compensation is reached and        aggressive resuscitation is required to prevent death.

The above SBSS scale can be used to define whether or not a bleeding iseligible for an investigation trial, depending on the alleged efficacyof the product to be tested.

Based on surgeon key opinion leaders (KOL) feedback, life-threateningbleeding (score of 4 or 5) is applicable for trauma surgeries orbattlefield wounds and would thus usually not be included in clinicalinvestigation of a hemostatic product as an eligible bleeding site. Flowrates for a surface bleeding severity score of 5 do reflectlife-threatening bleeding, but it would be highly unlikely that thislevel of bleeding would ever be seen in elective surgical cases. Infact, surgeon key opinion leaders also suggested that surface bleedingseverity scores 4 and 5 are infrequent occurrences for elective cases.

After having defined such a qualitative scale, the simulating device canbe used to determine thresholds for the flow rates of the blood liquidcorresponding to each one of the scores of the surface bleeding severityscale. This enables building a quantitative definition in addition tothe qualitative definition above.

To this end, a surgeon will assess the bench-top model under each of thethree target bleeding sites (TBS) scenarios, i.e. by using each of theabove described TBS plates with reference to FIGS. 6a, 6b, 7a, 7b, 8aand 8 b.

Establishing the relationship between the scores of the surface bleedingseverity scale and flow rates of the blood liquid in the simulatingdevice will for example proceed in two steps.

First, the surgeon will observe a continuous slowly increasing inflowrate and will identify likely targets for thresholds of the surfacebleeding scoring system.

After these initial thresholds are identified, the surgeon will thenrefine the definition of the scoring system by observing 10 bleedingscenarios at uniformly distributed increments of flow rate within eachinitially defined interval.

For example, during the initial observation of the continuallyincreasing pump flow rate, the surgeon may identify the followingthresholds as likely candidates for changes in the SBSS: 0, 1.0 ml/min,3.0 ml/min, 5.0 ml/min, 15.0 ml/min, and 50.0 ml/min.

Following this, the surgeon will observe 10 equally distributed pumpflow rates within each initially identified interval.

In the context of the hypothetical example above, for the interval (0ml/min and 1.0 ml/min], the surgeon will observe simulated bleeds ateach increment of 0.1 ml/min from 0 ml/min to 1.0 ml/min.

Thus there will be a total of 50 incremental scorings (10 for each ofthe 5 initially defined intervals).

At each increment the following steps can be used in the scoringprocess:

-   -   Step 1: The surgeon begins with a clean surface.    -   Step 2: Blood flow begins at the given flow rate.    -   Step 3: The surface is wiped clean, while the pump continues to        flow at the given rate.    -   Step 4: After observing the blood flow from the newly cleaned        surface during a certain amount of time (e.g. from 1 second to        60 seconds, and preferably during at least 10 seconds), the        surgeon assigns one of the defined score of the surface bleeding        severity scale.

When it is desired to check if the out-flow rates are well correlatedwith the in-flow rates, one can also perform the following additionalsteps:

-   -   Step 5: The surface is wiped clean, while the pump continues to        flow at the given rate.    -   Step 6: Immediately following the cleaning, a 4×4 inch stack of        pre-weighed gauze is applied to the surface and kept in place        for 5 seconds.    -   Step 7: Immediately after the gauze is removed, it is weighed to        determine post-bleed weight and determine the out-flow rate.

To check if out-flow rates are well correlated with the in-flow rates,one can then measure, for each in-flow rate and TBS plate combinationconsidered, the out-flow rate obtained from the weighing of the gauzeimmediately following the time that the surface bleeding severity scorewas assigned by the surgeon (step 7).

By subtraction of initial gauze stack, weight of blood alone is obtainedwhich when combined with area and time of gauze application will providea measurement of bleeding out-flow rate. Each out-flow measurement isthen regressed against the in-flow rate using a linear regression modeland the correlation coefficient and corresponding 95% confidenceinterval is reported.

Because the flow rate on the pump in this scenario is monotonicallyincreased, the resulting refined surface bleeding severity scores willreflect a 6-interval partition of the flow rate range with eachpartition corresponding to a given surface bleeding severity score.

In the entire description, the notations of any range—also calledinterval—follow the following rules:

-   -   a range noted [x;y] means that both values x and y are included        in the range;    -   a range noted]x;y[ means that both values x and y are excluded        from the range;    -   a range noted]x;y] means that value x is excluded from the range        whereas value y is included in the range;    -   a range noted [x;y[ means that value x is included in the range        whereas value y is excluded from the range.

The entire procedure outlined above is then repeated for each of thethree TBS scenarios, thus resulting in a total of 50 scorings and 50observed outflow gauze weights for each scenario.

The surgeon performing the whole procedure can then define a flow raterange for each of the TBS plates, thus establishing a relationshipbetween the input flow rate of the blood liquid (possibly correcteddepending on the results of the correlation with the output flow) andeach of the scores defining the surface bleeding severity scale (6discrete scores in the example above).

These ranges for each of the TBS plate can be used as such.

Table 2 below gives a first example (Example A) intervals defined by theexpert surgeon performing the procedure, depending on the TBS platesused.

TABLE 2 Flow rates (mL/min) intervals associated to Example A TBS Score0 Score 1 Score 2 Score 3 Score 4 Score 5 Final  1 cm² 0 ]0; 0.9[ [0.9;5.6[ [5.6; 13.0[ [13.0; 70.0[ [70.0; +∞[ intervals by 10 cm² 0 ]0; 1.5[[1.5; 5.5[ [5.5; 13.0[ [13.0; 70.0[ [70.0; +∞[ surface area 50 cm² 0 ]0; 12.0[ [12.0; 25.0[ [25.0; 50.0[   [50.0; 166.0[ [166.0; +∞[ 

Table 3 below gives a second example (Example B) of intervals defined bythe expert surgeon performing the procedure, depending on the TBS platesused.

TABLE 3 Flow rates (mL/min) intervals associated to Example B TBS Score0 Score 1 Score 2 Score 3 Score 4 Score 5 Final  1 cm² 0 ]0; 4.8[ [4.8;12.0[ [12.0; 25.3[ [25.3; 102.0[ [102.0; +∞[ intervals by 10 cm² 0 ]0;9.1[ [9.1; 20.0[ [20.0; 71.3[ [71.3; 147.4[ [147.4; +∞[ surface area 50cm² 0  ]0; 13.5[ [13.5; 28.0[   [28.0; 117.3[ [117.3; 192.7[  [192.7;+∞[

According to another embodiment, the interval thresholds correspondingto each surface bleeding severity score are averaged across the threeTBS scenarios. This enables defining a single relationship between flowrate and the surface bleeding severity score across all TBS scenarios.

For example, supposing that the resulting flow rate intervalcorresponding to a surface bleeding severity score of 1 is]x1 ml/min, y1ml/min[,]x2 ml/min, y2 ml/min[, and]x3 ml/min, y3 ml/min[, within the 1,10, and 50 cm² TBS scenarios, respectively. Then the final resultingflow rate interval for a SBSS of 1 will be](x1+x2+x3)/3 ml/min,(y1+y2+y3)/3 ml/min[. The result of this averaging can define a singlesurface bleeding severity score system that could be applied across allTBS scenarios in subsequent phases of a medical investigation.

In case the procedure is performed by several expert surgeons, intervalscould also be averaged based on the intervals defined by each expertsurgeon for each severity score for each plate.

According to another embodiment, the expert surgeon determines anddefines the intervals for one of the TBS plate, those intervals beingthen processed to derive the corresponding intervals for the other TBSplates depending on the pattern of holes for the TBS plate. Theintervals are thus normalized for each of the surface area of the TBSplate used for the experiment.

Table 4 below gives an example of normalized intervals assigned todifferent TBS plates, those normalized intervals being also derived fromthe intervals defined for the 1 cm² TBS plate. In this third example(Example C), the intervals with values rounded to the above superiorunit are assigned to the TBS plate of 1 cm² and the intervals for theother TBS plates are calculated taking into account the enlargement ofthe surface area compared to the 1 cm² TBS area. The normalizationfactor is given by the formula 1+2%*[percentage_of_enlargement] and thefinal limit of the intervals corresponds to the factorized value roundedto the above superior unit.

TABLE 4 Flow rates (mL/min) intervals associated to Example C TBS Score0 Score 1 Score 2 Score 3 Score 4 Score 5 Intervals defined by 0  ]0;4.8[ [4.8; 12.0[ [12.0; 25.3[ [25.3; 102.0[ [102.0; +∞[  expert surgeonfor 1 cm² TBS Final  1 cm² 0 ]0; 5[ [5; 12[ [12; 26[ [26; 102[ [102; +∞[normalized 10 cm² 0 ]0; 6[ [6; 15[ [15; 31[ [31; 123[ [123; +∞[intervals by 50 cm² 0  ]0; 10[ [10; 24[  [24; 51[ [51; 204[ [204; +∞[surface area

Fixing the intervals corresponding to each of the scores of the surfacebleeding scale, possibly depending on the TBS plate used in thesimulating device, gives a quantitative final definition of the surfacebleeding severity scale that can be simulated in the simulating device.

Learning of the Surface Bleeding Severity Scale

As mentioned, the simulating device enables simulation of specificsurface bleeding at given flow rate in a precise and repeatable manner,which is very advantageous as it will help surgeons/investigators to betrained and tested to learn the specifically defined surface bleedingseverity scale.

In particular, the device for simulating the surface bleeding can beused to create training and/or testing videos of bleeding scenariosacross the range of surface bleeding severity values as definedpreviously for each TBS plate.

According to a non-limitative example, for each TBS scenario, two videosare created for each of five flow rates uniformly distributed within theinterval partition defining each surface bleeding severity value.

For example, if the flow rate interval corresponding to a surfacebleeding severity value of 3 is defined to be [3.0 ml/min, 5.0 ml/min[,two separate videos of surface bleedings at each flow rates of 3.4, 3.8,4.2, 4.4, and 4.6 ml/min are made for each TBS scenario.

The procedures for recording the video sessions can be similar as thescoring process given above (Step 1 to Step 4). Specifically, the videowill begin when blood begins to flow at Step 2 and will continue to runthrough Step 4. In a preferred embodiment, the video recording of Step 4following the clean wiping of the TBS surface of Step 3 is done during aperiod of time between 12 seconds and 20 seconds. The relevant part ofthe video for assessment of the surface bleeding severity scorecorresponds in this case to the first 10 seconds following the cleanwiping of the TBS surface of Step 3.

The videos for the surface bleeding severity score of 0 (completehemostasis) are made by considering 5 scenarios within each TBSscenarios. The 5 scenarios aim at depicting differing flow rates priorto achieving hemostasis. In particular, the midpoint of the flow rateinterval for each surface bleeding severity score ranging from 1 to 5 isconsidered.

For example, if the flow rate interval corresponding to a surfacebleeding severity score of 3 is defined to be [3.0 ml/min, 5.0 ml/min[,we consider an initial flow rate of 4.0 ml/min. In this case, the videobegins at Step 2 defined above when blood begins to flow at a flow rateof 4.0 ml/min. Prior to the surface being wiped clean in Step 3, thepump is turned off (flow rate of 0.0 ml/min), and the video continues torun for at least another 10 seconds, preferably between 12 seconds and20 seconds. Again, the relevant part of the video for assessment of thesurface bleeding severity score corresponds to the first 10 secondsfollowing the clean wiping of the TBS surface of Step 3.

With such an example of procedure, a total of 180 videos are createdcorresponding to two replicates at each of 5 flow rates for each of the6 surface bleeding severity scores, across the 3 TBS scenarios(2×5×6×3=180).

The first set of replicates can serve as the training pool from which atraining sample is created, while the second set of replicates serves asa test pool from which the test sample is created. Alternatively, onlyone pool of videos is recorded, which will be used both in the trainingsessions and in the test sessions.

Consequently, to prepare for the training and/or testing of thesurgeons/investigators that have to learn the surface bleeding severityscale (for example to be part of a medical investigation to assess anhemostatic product), several sets of surface bleedings are simulated—andpreferably at least partially recorded as a video—with the abovedescribed simulating device, wherein a set of surface bleedings issimulated for each degree of severity of surface bleeding, based on thesurface bleeding severity scale, depending on the ranges of blood flowrates defining each score of the surface bleeding severity scale.

For example, based on the surface bleeding severity scale as defined bythe averaged intervals above, several sets of surface bleedings aresimulated—and preferably at least partially recorded as a video—with theabove described simulating device, wherein:

-   -   a first set of surface bleedings is simulated to represent a        first degree of severity of surface bleeding, each of the        surface bleedings being simulated by adjusting the flow of the        blood liquid provided by the pump system 2 to a specific value        being chosen superior to 0 mL/min and inferior to 4.8 mL/min;    -   a second set of surface bleedings is simulated to represent a        second degree of severity of surface bleeding, each of the        surface bleedings being simulated by adjusting the flow of the        blood liquid provided by the pump system 2 to a specific value        being chosen superior or equal to 4.8 mL/min and inferior to        12.0 mL/min;    -   a third set of surface bleedings is simulated to represent a        third degree of severity of surface bleeding, each of the        surface bleedings being simulated by adjusting the flow of the        blood liquid provided by the pump system 2 to a specific value        being chosen superior or equal to 12.0 mL/min and inferior to        25.3 mL/min;    -   a fourth set of surface bleedings is simulated to represent a        fourth degree of severity of surface bleeding, each of the        surface bleedings being simulated by adjusting the flow of the        blood liquid provided by the pump system 2 to a specific value        being chosen superior or equal to 25.3 mL/min and inferior to        102.0 mL/min;    -   a fifth set of surface bleedings is simulated to represent a        fifth degree of severity of surface bleeding, each of the        surface bleedings being simulated by adjusting the flow of the        blood liquid provided by the pump system 2 to a specific value        being chosen superior or equal to 102.0 mL/min.

According to another example, based on the surface bleeding severityscale as defined by the expert surgeon as summarized in Table 3 above,several sets of surface bleedings are simulated—and preferably at leastpartially recorded as a video—with the above described simulatingdevice, wherein:

-   -   a first set of surface bleedings is simulated to represent a        first degree of severity of surface bleeding, said first set of        surface bleedings comprising        -   at least one surface bleeding being simulated by mounting a            plate 32 with through holes 321 arranged according to a            pattern of 1 cm² and by adjusting the flow of the blood            liquid provided by the pump system 2 to a specific value            being chosen superior to 0 mL/min and inferior to 4.8            mL/min;        -   at least one surface bleeding being simulated by mounting a            plate 32 with through holes 321 arranged according to a            pattern of 10 cm² and by adjusting the flow of the blood            liquid provided by the pump system 2 to a specific value            being chosen superior to 0 mL/min and inferior to 9.1            mL/min;        -   at least one surface bleeding being simulated by mounting a            plate 32 with through holes 321 arranged according to a            pattern of 50 cm² and by adjusting the flow of the blood            liquid provided by the pump system 2 to a specific value            being chosen superior to 0 mL/min and inferior to 13.5            mL/min;    -   a second set of surface bleedings is simulated to represent a        second degree of severity of surface bleeding, said second set        of surface bleedings comprising        -   at least one surface bleeding being simulated by mounting a            plate 32 with through holes 321 arranged according to a            pattern of 1 cm² and by adjusting the flow of the blood            liquid provided by the pump system 2 to a specific value            being chosen superior or equal to 4.8 mL/min and inferior to            12.0 mL/min;        -   at least one surface bleeding being simulated by mounting a            plate 32 with through holes 321 arranged according to a            pattern of 10 cm² and by adjusting the flow of the blood            liquid provided by the pump system 2 to a specific value            being chosen superior or equal to 9.1 mL/min and inferior to            20.0 mL/min;        -   at least one surface bleeding being simulated by mounting a            plate 32 with through holes 321 arranged according to a            pattern of 50 cm² and by adjusting the flow of the blood            liquid provided by the pump system 2 to a specific value            being chosen superior or equal to 13.5 mL/min and inferior            to 28.0 mL/min;    -   a third set of surface bleedings is simulated to represent a        third degree of severity of surface bleeding, said third set of        surface bleedings comprising        -   at least one surface bleeding being simulated by mounting a            plate 32 with through holes 321 arranged according to a            pattern of 1 cm² and by adjusting the flow of the blood            liquid provided by the pump system 2 to a specific value            being chosen superior or equal to 12.0 mL/min and inferior            to 25.3 mL/min;        -   at least one surface bleeding being simulated by mounting a            plate 32 with through holes 321 arranged according to a            pattern of 10 cm² and by adjusting the flow of the blood            liquid provided by the pump system 2 to a specific value            being chosen superior or equal to 20.0 mL/min and inferior            to 71.3 mL/min;        -   at least one surface bleeding being simulated by mounting a            plate 32 with through holes 321 arranged according to a            pattern of 50 cm² and by adjusting the flow of the blood            liquid provided by the pump system 2 to a specific value            being chosen superior or equal to 28.0 mL/min and inferior            to 117.3 mL/min;    -   a fourth set of surface bleedings is simulated to represent a        fourth degree of severity of surface bleeding, said fourth set        of surface bleedings comprising        -   at least one surface bleeding being simulated by mounting a            plate 32 with through holes 321 arranged according to a            pattern of 1 cm² and by adjusting the flow of the blood            liquid provided by the pump system 2 to a specific value            being chosen superior or equal to 25.3 mL/min and inferior            to 102.0 mL/min;        -   at least one surface bleeding being simulated by mounting a            plate 32 with through holes 321 arranged according to a            pattern of 10 cm² and by adjusting the flow of the blood            liquid provided by the pump system 2 to a specific value            being chosen superior or equal to 71.3 mL/min and inferior            to 147.4 mL/min;        -   at least one surface bleeding being simulated by mounting a            plate 32 with through holes 321 arranged according to a            pattern of 50 cm² and by adjusting the flow of the blood            liquid provided by the pump system 2 to a specific value            being chosen superior or equal to 117.3 mL/min and inferior            to 192.7 mL/min;    -   a fifth set of surface bleedings is simulated to represent a        fifth degree of severity of surface bleeding, said fifth set of        surface bleedings comprising        -   at least one surface bleeding being simulated by mounting a            plate 32 with through holes 321 arranged according to a            pattern of 1 cm² and by adjusting the flow of the blood            liquid provided by the pump system 2 to a specific value            being chosen superior or equal to 102.0 mL/min;        -   at least one surface bleeding being simulated by mounting a            plate 32 with through holes 321 arranged according to a            pattern of 10 cm² and by adjusting the flow of the blood            liquid provided by the pump system 2 to a specific value            being chosen superior or equal to 147.4 mL/min;        -   at least one surface bleeding being simulated by mounting a            plate 32 with through holes 321 arranged according to a            pattern of 50 cm² and by adjusting the flow of the blood            liquid provided by the pump system 2 to a specific value            being chosen superior or equal to 192.7 mL/min.

The definition of the different sets of surface bleedings to besimulated—and preferably at least partially recorded as a video—for thesurface bleeding severity scale as defined by the intervals summarizedin Table 2 or in Table 4 above can be easily extrapolated from the aboveprocedure as described with reference to the intervals of Table 3.

After having simulated and recorded all the required sets of surfacebleedings, at least one set of training videos is made with the pool oftraining videos and one set of testing videos is made with the pool oftesting videos.

The set of training videos can be prepared by selecting 36 videos fromthe pool of training videos, where for instance, within each TBS, twovideos are sampled for each surface bleeding severity value.

Because the surface bleeding severity score represents a discretizationof a continuum of flow rates, videos within each surface bleedingseverity value are preferably sampled in order to be representative ofbleeds occurring in the flow rate interval corresponding to that value.

For example, the two videos for each surface bleeding severity value aresampled such that the three videos of flow rates near the midpoint ofthe flow rate interval have a 90% chance of being sampled (30% each)while the videos near the endpoints of the flow rate interval have a 10%chance of being sampled (5% each).

For example, if the flow rate interval corresponding to a surfacebleeding severity value of 3 is defined to be [3.0 ml/min, 5.0 ml/min[,videos of bleeding at flow rates of 3.4, 3.8, 4.2, 4.4, and 4.6 ml/minwill be available for sampling into the training set. In this case, twovideos are randomly sampled (without replacement) from these five videosin such a way that the videos corresponding to flow rates 3.8, 4.2, and4.4 ml/min each have a 30% chance of being chosen, while the videos ofbleeding flow rates of 2.4 and 4.6 ml/min will each have a 5% chance ofbeing chosen.

This sampling is done for each score within each TBS, resulting in 12videos for each TBS and 36 training videos in total.

The testing videos are sampled from the pool of testing videos createdbefore. The testing videos are preferably sampled in the same manner asthat described for the training videos. Specifically, the two videos foreach surface bleeding severity value are sampled such that the threevideos of flow rates near the midpoint of the flow rate interval have a90% chance of being sample (30% each) while the videos near theendpoints of the flow rate interval have a 10% chance of being sampled(5% each). Even though the sampling method is the same as for thetraining videos, the result of the sampling for the testing videos islikely to be different from the result of the sampling for the trainingvideos.

Such sampling also enables having a selection of 36 testing videos intotal.

Instead of simulating and recording two videos of five flow ratesuniformly distributed within the interval partition defining eachsurface bleeding severity score as described above (180 videos in total)and then performing a sampling among those videos to get 36 trainingvideos and 36 testing videos, it is possible to first perform a samplingthat will dictate—for each surface bleeding severity score and for eachTBS—which two flow rates have to be used for simulation of a surfacebleeding. Consequently, only the flow rates selected from the samplingare simulated and recorded in a video. With such an alternativeprocedure, a total of 72 videos are created corresponding to tworeplicates (one for the training and one for the testing) at each of 2flow rates for each of the 6 surface bleeding severity scores, acrossthe 3 TBS scenarios (2×2×6×3=72).

For the training, the 36 training videos are preferably organized as atraining set where the videos are presented separately for each TBSsetting and in increasing order of flow rates. In this way, surgeons aretrained to visual increases in bleeding flow rates and associate themwith increases in the surface bleeding severity value.

Following the training, each surgeon is then shown a set of testingvideos that is different from the one used in the training phase.

One or several testing sets of videos can be prepared, based on the 36testing videos resulting from the sampling as described above, where theselected testing videos are fully randomized.

Each video of the selected testing videos can be displayed severaltimes.

According to a first example, the testing set of videos is created bydisplaying, in a random order, 3 times the 36 selected testing videos.Such example of testing set of videos thus comprises a sequence of 108testing videos displayed randomly.

According to a second example, the testing set of videos is created bydisplaying, in a random order, the 36 selected testing videos and the 6testing videos selected from the sampling for each TBS corresponding tothe score 0. Such example of testing set of videos thus comprises asequence of 42 testing videos displayed randomly.

Preferably, the testing sets of videos are prepared to comprise the samenumber of videos for each score of the surface bleeding scale. Possibly,the number of testing videos for the score 0 is larger than for theother scores of the surface bleeding scale.

Several different testing sets of videos can be prepared where the orderof the selected testing videos to display is different.

Before performing a clinical investigation for testing the hemostaticperformance of a product, each surgeon to be enrolled in theinvestigation as an investigator is trained and tested to be sure thathe will be able to assess the severity of a surface bleeding accordingto the definition of the scores.

First an explanation of the surface bleeding severity scale andcorresponding visual descriptors will be given to the investigators,based for instance on the information as given in Table 1 above.

Possibly, a preparatory set of videos are displayed to the investigator,where the videos show the plates 32 that have been used for simulatingthe different surface bleedings used in the training and testing videoswithout any flow of blood liquid.

After having watched the set of 36 training videos, the investigatorsare tested with a testing set of videos (e.g. a testing set of 42 videosor a testing set of 108 videos). For each videos of the set of testingvideos, they are asked to assign a single surface bleeding severityscore.

Enrollment of the investigators in the clinical investigation depends ontheir success in the recognition of the surface bleeding severity of thetesting videos, which success depends on the degree of knowledgenecessary for the clinical investigation.

The clinical investigation is indeed always based on the surfacebleeding severity scale of reference, on which the investigators havebeen trained and tested, but the criterion for recognizing the severityof the surface bleeding can differ from a clinical investigation toanother.

For instance, in a possible example of clinical investigation, bleedingseventies with a surface bleeding severity score of 1, 2, or 3 will beeligible for inclusion into the clinical trial, whereas bleeding scoresof 0, 4, and 5 will not be eligible for inclusion. In addition, surfacebleeding severity scores will also determine hemostasis (success) versusnon-hemostasis (failure). A score of 0 will define hemostasis and asurface bleeding severity score larger than 0 will be equivalent tonon-hemostasis (failure). Such example of rules for the clinicalinvestigation is summarized in Table 5 below.

TABLE 5 Surface Bleeding Severity Score 0 1 2 3 4 5 Verbal DescriptorNone Minimal Mild Moderate Severe Extreme of the bleeding VisualDescriptor Dry Oozing Pooling Flowing Streaming Gushing of the bleedingExpected None Manual Manual Manual Manual Manual Intervention(s)pressure, pressure, pressure, pressure, pressure, cautery, cautery,cautery, cautery, cautery, adjuvant suture, suture, suture, suture,hemostat(s) adjuvant adjuvant staples, staples, hemostat(s) hemostat(s)tissue repair tissue repair Eligible for No Yes Yes Yes No No EnrollmentHemostatic Yes No No No No No Success

With such proposed clinical investigation, the test of each investigatorwill be evaluated for determining the percentage of correctidentification of study eligibility and the percentage of correctidentification of hemostatic success.

Since it is important for investigators to be able to distinguishbetween an eligible versus ineligible bleeding site at baseline, andhemostasis versus non-hemostasis, a minimum score for these parametersmust be achieved prior to approval for participation in the clinicalinvestigation and enrollment of subjects. The minimum rate of positiverecognitions may be for instance equal to 90%.

If an investigator fails, re-training and re-testing will be conducted.Preferably, an investigator has three tries to meet the minimum scorefor both parameters. The minimum score for both parameters must beachieved within a single test. If the investigator is unable to achievethe minimum score after 3 attempts, he/she will not be permitted toparticipate in the clinical investigation.

Clinical Investigation for Assessment of a Hemostatic Product

Once the investigators have been trained and successfully tested, theycan perform the clinical procedure which has been defined for testingthe hemostatic product under investigation.

Below is described an example of a possible procedure for assessment ofthe efficacy of a hemostatic product, also referred to a hemostaticimplant material.

Although the properties of the ideal local hemostatic agent may varyaccording to the surgical specialty, some properties are universallyvalued including: rapid and effective control/cessation of bleeding;ability to make effective contact with the bleeding surface; acceptablesafety profile; and reliable, easy to handle, quick to prepare.

Assessment of the safety and efficacy of a hemostat can be done byperforming a specific clinical investigation.

Before the investigation, the investigators are trained on theappropriate application of the hemostatic product.

Subjects undergoing any surgical procedure could be eligible forenrolment into the clinical investigation. This could concern subjectsundergoing either open or laparoscopic surgeries, like for instancecardiothoracic, abdominal, spinal, soft tissue, breast, or orthopediclower extremity surgeries.

The Investigator will perform the surgery per his or her standardprocedures, including conventional methods of hemostasis (pressure,ligature, cautery, etc.). Before the surgical procedure, a hemostaticproduct to be tested will be prepared per the corresponding instructionsfor use.

A study-specific stopwatch is preferably used to track hemostatapplication and the times of hemostasis evaluation.

Hemostasis is evaluated by the investigator using the specific surfacebleeding severity scale that he has learned.

A score will be assigned at successive time points until hemostasis isachieved, for instance at the following time points:

Baseline—when evaluating intraoperative eligibility;

1^(st) time point (e.g. at 3 minutes);

2^(nd) time point (e.g. at 6 minutes); and

3^(rd) time point (e.g. at 10 minutes).

Bleeding severity assessments can be made by one or more investigators,but has to be done independently.

In case of an assessment by two investigators, it is considered thatthere is hemostasis if both investigators assign a score of 0 at thesame assessment time point. All other scores are considered as a failureof hemostasis. The target bleeding site will be assessed at every timepoint, up until hemostasis is achieved.

In cases where hemostasis is not achieved at the last time point, theinvestigator may use whatever means necessary in order to controlbleeding.

The efficacy of the hemostatic product under investigation is thenassessed by processing and comparing all the data gathered during theprocedure.

In addition to the advantages mentioned above, the device and method forsimulation of surface bleedings presented in this document can help thesurgeons to establish their diagnostics in respect of the severity ofthe bleedings, and thus help them making their choice of the hemostaticagent to use in an easier and faster way.

The proposed device and method for simulation of surface bleedings alsoparticipate to the harmonization in the surface bleedings recognition,and thus to the harmonization of the diagnostic methods and practiceamong surgeons, which is generally positive for the health of thepatient.

Another advantage of the proposed device and method for simulation ofsurface bleedings is that it could prevent performing in vivo studies onanimals for testing of an hemostatic product, which has therefore a verypositive ethical effect.

BIBLIOGRAPHIC REFERENCES

-   “Acute in-vivo evaluation of bleeding with Gelfoam plus saline and    Gelfoam plus human thrombin using a liver square lesion model in    swine” (J Thromb Thrombolysis. 2009 July; 28(1):1-5. doi:    10.1007/s11239-008-0249-3. Epub 2008 Jul. 16)

1. A device to simulate a surface bleeding, comprising: A source of ablood liquid, in particular a synthetic blood liquid or a blood liquidhaving been removed from a human body; A pump system connected to thesource of blood liquid and configured to provide a controlled flow ofsaid blood liquid; A wound simulator having an open chamber connected tothe pump system to receive the controlled flow of blood liquid, whereinthe wound simulator comprises a set of interchangeable plates, eachplate having a plurality of holes arranged through said plate accordingto a specific pattern, wherein the specific pattern is different foreach plate of the set of interchangeable plates, and each plate beingadapted to be removably mounted on the wound simulator to close the openchamber, so that blood liquid flows out of the chamber through the holesof the plate mounted on the wound simulator.
 2. The device of claim 1,wherein the plates of the set of interchangeable plates have holesarranged according to specific patterns of different surface areas. 3.The device of claim 1, wherein the plates of the set of interchangeableplates have holes arranged according to specific patterns of differentsizes.
 4. The device of claim 1, wherein the holes are provided in eachof the interchangeable plates at a density of at least 50 holes/cm². 5.The device of claim 1, wherein the holes are provided in each of theinterchangeable plates at a density of 100 holes/cm².
 6. The device ofclaim 1, wherein the number and diameter of the holes provided in eachof the interchangeable plates are set to reproduce the visual appearanceof a bleeding surface.
 7. The device of claim 6, wherein the holesprovided in each one of the interchangeable plates have all the samediameter, said diameter being comprised between 0.2 mm and 1 mm.
 8. Thedevice of claim 6, wherein the holes provided in each one of theinterchangeable plates have all the same diameter, said diameter beingof 0.5 mm.
 9. The device of claim 1, wherein the holes provided in eachone of the interchangeable plates are regularly spaced apart in thecorresponding specific pattern, with a pitch comprised between 0.4 mmand 2 mm.
 10. The device of claim 1, wherein the holes provided in eachone of the interchangeable plates are regularly spaced apart in thecorresponding specific pattern, with a pitch of 1 mm.
 11. The device ofclaim 1, wherein the wound simulator further comprises a gravity fedgutter system to drain out the blood liquid having passed through theholes of the plate and guide it into a receiving container.
 12. Thedevice of claim 1, further comprising a pressure monitoring systemconnected to the pump system to measure the pressure of the blood liquidsupplied to the chamber of the wound simulator.
 13. The device of claim1, wherein the pump system comprises a peristaltic pump provided withtubing for circulation of the blood liquid from the blood source to theopen chamber.
 14. The device of claim 1, wherein the pump systemcomprises a pump controller for control of the flow of the blood liquidfrom the blood source to the open chamber.
 15. A method for simulating aplurality of different surface bleedings with the device comprising: Asource of a blood liquid, in particular a synthetic blood liquid or ablood liquid having been removed from a human body; A pump systemconnected to the source of blood liquid and configured to provide acontrolled flow of said blood liquid; A wound simulator having an openchamber connected to the pump system to receive the controlled flow ofblood liquid, wherein the wound simulator comprises a set ofinterchangeable plates, each plate having a plurality of holes arrangedthrough said plate according to a specific pattern, wherein the specificpattern is different for each plate of the set of interchangeableplates, and each plate being adapted to be removably mounted on thewound simulator to close the open chamber, so that blood liquid flowsout of the chamber through the holes of the plate mounted on the woundsimulator, wherein each surface bleeding is simulated by mounting on thewound simulator a specific plate chosen among the set of interchangeableplates, and adjusting the flow of blood liquid provided by the pumpsystem to a specific value.
 16. The method of claim 15, comprising thesimulation of several sets of surface bleedings, wherein: a first set ofsurface bleedings is simulated to represent a first degree of severityof surface bleeding, each of the surface bleedings being simulated byadjusting the flow of the blood liquid provided by the pump system to aspecific value being chosen superior to 0 mL/min and inferior to 4.8mL/min; a second set of surface bleedings is simulated to represent asecond degree of severity of surface bleeding, each of the surfacebleedings being simulated by adjusting the flow of the blood liquidprovided by the pump system to a specific value being chosen superior orequal to 4.8 mL/min and inferior to 12.0 mL/min. a third set of surfacebleedings is simulated to represent a third degree of severity ofsurface bleeding, each of the surface bleedings being simulated byadjusting the flow of the blood liquid provided by the pump system to aspecific value being chosen superior or equal to 12.0 mL/min andinferior to 25.3 mL/min. a fourth set of surface bleedings is simulatedto represent a fourth degree of severity of surface bleeding, each ofthe surface bleedings being simulated by adjusting the flow of the bloodliquid provided by the pump system to a specific value being chosensuperior or equal to 25.3 mL/min and inferior to 102.0 mL/min. a fifthset of surface bleedings is simulated to represent a fifth degree ofseverity of surface bleeding, each of the surface bleedings beingsimulated by adjusting the flow of the blood liquid provided by the pumpsystem to a specific value being chosen superior or equal to 102.0mL/min.
 17. The method of claim 15, comprising the simulation of severalsets of surface bleedings, wherein: a first set of surface bleedings issimulated to represent a first degree of severity of surface bleeding,said first set of surface bleedings comprising at least one surfacebleeding being simulated by mounting a plate with through holes arrangedaccording to a pattern of 1 cm² and by adjusting the flow of the bloodliquid provided by the pump system to a specific value being chosensuperior to 0 mL/min and inferior to 4.8 mL/min; at least one surfacebleeding being simulated by mounting a plate with through holes arrangedaccording to a pattern of 10 cm² and by adjusting the flow of the bloodliquid provided by the pump system to a specific value being chosensuperior to 0 mL/min and inferior to 9.1 mL/min; at least one surfacebleeding being simulated by mounting a plate with through holes arrangedaccording to a pattern of 50 cm² and by adjusting the flow of the bloodliquid provided by the pump system to a specific value being chosensuperior to 0 mL/min and inferior to 13.5 mL/min; a second set ofsurface bleedings is simulated to represent a second degree of severityof surface bleeding, said second set of surface bleedings comprising atleast one surface bleeding being simulated by mounting a plate withthrough holes arranged according to a pattern of 1 cm² and by adjustingthe flow of the blood liquid provided by the pump system to a specificvalue being chosen superior or equal to 4.8 mL/min and inferior to 12.0mL/min; at least one surface bleeding being simulated by mounting aplate with through holes arranged according to a pattern of 10 cm² andby adjusting the flow of the blood liquid provided by the pump system toa specific value being chosen superior or equal to 9.1 mL/min andinferior to 20.0 mL/min; at least one surface bleeding being simulatedby mounting a plate with through holes arranged according to a patternof 50 cm² and by adjusting the flow of the blood liquid provided by thepump system to a specific value being chosen superior or equal to 13.5mL/min and inferior to 28.0 mL/min; a third set of surface bleedings issimulated to represent a third degree of severity of surface bleeding,said third set of surface bleedings comprising at least one surfacebleeding being simulated by mounting a plate with through holes arrangedaccording to a pattern of 1 cm² and by adjusting the flow of the bloodliquid provided by the pump system to a specific value being chosensuperior or equal to 12.0 mL/min and inferior to 25.3 mL/min; at leastone surface bleeding being simulated by mounting a plate with throughholes arranged according to a pattern of 10 cm² and by adjusting theflow of the blood liquid provided by the pump system to a specific valuebeing chosen superior or equal to 20.0 mL/min and inferior to 71.3mL/min; at least one surface bleeding being simulated by mounting aplate with through holes arranged according to a pattern of 50 cm² andby adjusting the flow of the blood liquid provided by the pump system toa specific value being chosen superior or equal to 28.0 mL/min andinferior to 117.3 mL/min; a fourth set of surface bleedings is simulatedto represent a fourth degree of severity of surface bleeding, saidfourth set of surface bleedings comprising at least one surface bleedingbeing simulated by mounting a plate with through holes arrangedaccording to a pattern of 1 cm² and by adjusting the flow of the bloodliquid provided by the pump system to a specific value being chosensuperior or equal to 25.3 mL/min and inferior to 102.0 mL/min; at leastone surface bleeding being simulated by mounting a plate with throughholes arranged according to a pattern of 10 cm² and by adjusting theflow of the blood liquid provided by the pump system to a specific valuebeing chosen superior or equal to 71.3 mL/min and inferior to 147.4mL/min; at least one surface bleeding being simulated by mounting aplate with through holes arranged according to a pattern of 50 cm² andby adjusting the flow of the blood liquid provided by the pump system toa specific value being chosen superior or equal to 117.3 mL/min andinferior to 192.7 mL/min; a fifth set of surface bleedings is simulatedto represent a fifth degree of severity of surface bleeding, said fifthset of surface bleedings comprising at least one surface bleeding beingsimulated by mounting a plate with through holes arranged according to apattern of 1 cm² and by adjusting the flow of the blood liquid providedby the pump system to a specific value being chosen superior or equal to102.0 mL/min; at least one surface bleeding being simulated by mountinga plate with through holes arranged according to a pattern of 10 cm² andby adjusting the flow of the blood liquid provided by the pump system toa specific value being chosen superior or equal to 147.4 mL/min; atleast one surface bleeding being simulated by mounting a plate withthrough holes arranged according to a pattern of 50 cm² and by adjustingthe flow of the blood liquid provided by the pump system to a specificvalue being chosen superior or equal to 192.7 mL/min.
 18. The method ofclaim 15, wherein each of the simulated surface bleedings is recorded asa video.
 19. A method of preparation of at least a training set ofvideos comprising the following subsequent steps: Selecting a pluralityof videos of simulated surface bleedings and affecting to each one ofthe selected videos a score corresponding to a degree of severity ofsurface bleeding, wherein each video is a recording of a specificsurface bleeding simulated with a device comprising: A source of a bloodliquid, in particular a synthetic blood liquid or a blood liquid havingbeen removed from a human body; A pump system connected to the source ofblood liquid and configured to provide a controlled flow of said bloodliquid; A wound simulator having an open chamber connected to the pumpsystem to receive the controlled flow of blood liquid, wherein the woundsimulator comprises a set of interchangeable plates, each plate having aplurality of holes arranged through said plate according to a specificpattern, wherein the specific pattern is different for each plate of theset of interchangeable plates, and each plate being adapted to beremovably mounted on the wound simulator to close the open chamber, sothat blood liquid flows out of the chamber through the holes of theplate mounted on the wound simulator, wherein each surface bleeding issimulated by mounting on the wound simulator a specific plate chosenamong the set of interchangeable plates, and adjusting the flow of bloodliquid provided by the pump system to a specific value, Classifying theselected videos in a specific order for visualization, wherein the scoreof each of the videos is to be displayed with the corresponding video.20. The method of claim 19, wherein the videos are classified forvisualization according an increasing or decreasing order of thecorresponding degrees of severity of surface bleeding.
 21. A method ofpreparation of at least a testing set of videos comprising the followingsubsequent steps: Selecting a plurality of videos of simulated surfacebleedings and affecting to each one of the selected videos a scorecorresponding to a degree of severity of surface bleeding, wherein eachvideo is a recording of a specific surface bleeding simulated with adevice comprising: A source of a blood liquid, in particular a syntheticblood liquid or a blood liquid having been removed from a human body; Apump system connected to the source of blood liquid and configured toprovide a controlled flow of said blood liquid; A wound simulator havingan open chamber connected to the pump system to receive the controlledflow of blood liquid, wherein the wound simulator comprises a set ofinterchangeable plates, each plate having a plurality of holes arrangedthrough said plate according to a specific pattern, wherein the specificpattern is different for each plate of the set of interchangeableplates, and each plate being adapted to be removably mounted on thewound simulator to close the open chamber, so that blood liquid flowsout of the chamber through the holes of the plate mounted on the woundsimulator, wherein each surface bleeding is simulated by mounting on thewound simulator a specific plate chosen among the set of interchangeableplates, and adjusting the flow of blood liquid provided by the pumpsystem to a specific value, Classifying the videos in a random order forvisualization, wherein the score of each of the videos is not to bedisplayed with the corresponding video.
 22. A method of preparation ofat least a training set of videos and at least a testing set of videosusing a plurality of videos of simulated surface bleedings, wherein eachvideo is a recording of a specific surface bleeding simulated with adevice comprising: A source of a blood liquid, in particular a syntheticblood liquid or a blood liquid having been removed from a human body; Apump system connected to the source of blood liquid and configured toprovide a controlled flow of said blood liquid; A wound simulator havingan open chamber connected to the pump system to receive the controlledflow of blood liquid, wherein the wound simulator comprises a set ofinterchangeable plates, each plate having a plurality of holes arrangedthrough said plate according to a specific pattern, wherein the specificpattern is different for each plate of the set of interchangeableplates, and each plate being adapted to be removably mounted on thewound simulator to close the open chamber, so that blood liquid flowsout of the chamber through the holes of the plate mounted on the woundsimulator, wherein each surface bleeding is simulated by mounting on thewound simulator a specific plate chosen among the set of interchangeableplates, and adjusting the flow of blood liquid provided by the pumpsystem to a specific value, wherein a score corresponding to a degree ofseverity of surface bleeding is affected to each one of the plurality ofvideos, comprising: preparing the training set of videos by selectingsome videos of the plurality of videos, and classifying the selectedvideos in a specific order for visualization, wherein the score andinformation on the specific chosen plate of each of the videos are to bedisplayed with the corresponding video; preparing the testing set ofvideos by selecting some videos of the plurality of videos, andclassifying the selected videos in a random order for visualization,wherein the score of each of the videos is not to be displayed with thecorresponding video, and wherein the selection and/or classification ofthe videos is different from the training set of videos.
 23. A method oftraining a person to recognize and classify a severity of a surfacebleeding comprising the step of displaying a plurality of trainingvideos in a specific order, wherein each one of the training videosshows a simulated surface bleeding and a score corresponding to theseverity of said simulated surface bleeding.
 24. The method of claim 23,wherein the training videos are displayed according to an increasing ordecreasing order of the corresponding degrees of severity of surfacebleeding.
 25. The method of claim 23, comprising a subsequent step oftesting the person in applying the following steps: displaying in arandom order a plurality of testing videos each numerically labeled insequence, wherein each one of the testing videos shows a simulatedsurface bleeding without any score corresponding to the severity of saidsimulated surface bleeding of simulated surface bleeding, and whereinthe testing videos are different from the training videos and/or used ina different order; requesting the person to give for each of the testingvideos a score representative of the severity of the correspondingsurface bleeding in the order of the numerically labeled sequence.
 26. Amethod of performing a clinical trial to assess hemostatic power of aproduct against surface bleeding, comprising the following steps: a)characterizing the severity of a baseline surface bleeding from a woundof a patient by affecting a score; b) applying the product on the woundaccording to a specific protocol of use of the product; c) at apredetermined time after step b), characterizing the severity of theremaining surface bleeding from the wound of the patient by affecting ascore.
 27. The method of claim 26, wherein steps b) and c) are repeatedseveral times after each characterization of the severity of theremaining surface bleeding in order to assess the hemostatic power ofthe product over time.